Cullinan Therapeutics, Inc. (CGEM) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. Welcome to the Cullinan Therapeutics Corporate Update Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would like now to turn the conference over to Chad Messer, Vice President of Investor Relations. Please go ahead.

Hello, everyone, and thank you all for joining us on today's call to discuss our expanded focus in autoimmune diseases based on the exciting potential of CLN-978, our CD19xCD3 T cell engager, along with our corporate name change to Cullinan Therapeutics. My name is Chad Messer, and I'm the Vice President of Investor Relations at Cullinan Therapeutics. Before we begin, I would like to remind you the safe harbor provisions outlined on Slide #2. During today's presentation, management will be making certain forward-looking statements, which are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties, which may cause actual results to differ materially from those contained in such forward-looking statements. These risks are described more fully in the company's filings made with the Securities and Exchange Commission including our Annual Report on Form 10-K. You are cautioned not to place any due reliance on these forward-looking statements. In addition, this call contains time-sensitive information accurate only as of the date of the live broadcast April 16, 2024. Cullinan undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this call. As shown on Slide 3, we will begin today's call with opening remarks regarding our expanded focus on autoimmune diseases and our corporate name change from Nadim Ahmed, Cullinan's Chief Executive Officer. Following Nadim, Dr. Jeff Jones, our Chief Medical Officer, will talk through the clinical officer patients with CLN-978 and B-cell Non-Hodgkin's lymphoma as well as our initial plans for development in autoimmune diseases. Nadim will then share an overview of the high unmet need and limited treatment options in autoimmune diseases. Lastly, Patrick Baeuerle, Cullinan's Co-Founder and Chief Scientific Adviser will join us, and we will open the call for Q&A. I will now turn the call over to Cullinan CEO, Nadim Ahmed. Nadim?

Thank you, Chad, and thank you, everyone, for joining our call this morning. As you can see on Slide 4, today, is a really exciting day for Cullinan Therapeutics, a new name for our company representing our strategic expansion into autoimmune diseases. This decision was primarily based on the promise of CLN-978, our CD19xCD3 T cell engager to address areas of unmet need across a broad range of autoimmune diseases. I will also point out that much of our discovery and development efforts to date have focused on the immuno-oncology space, and most of our molecules in our pipeline harness the immune system. At the same time, the biology of oncology and immunology has continued to converge. Therefore, expanding our presence into immunology is a very natural adjacency for us as a company and represents an excellent strategic fit. We have also made the decision to focus the development of CLN-978 moving forward exclusively on autoimmune diseases, beginning with systemic lupus erythematosus, or SLE, as our first indication. We're also very pleased today to share for the first time the exciting new data from our lymphoma study, showing sustained B cell depletion in patients, along with important clinical activity and favorable safety operations. In summary, we believe we have a unique opportunity with CLN-978, which has the potential to be a first in class, off-the-shelf disease-modifying treatment for a broad range of autoimmune diseases with a differentiated safety profile. We have also intentionally positioned ourselves with a robust cash runway. And now with the private placement that we announced this morning, we have even more resources available to fully unlock the value of CLN-978 with a cash run right now into 2028. Before I hand it over to our Chief Medical Officer, Dr. Jeff Jones, let me share a high-level overview of our CLN-978 program and our pipeline overall. Turning now to Slide 5. CLN-978 is a fully internally developed molecule and importantly, is a wholly owned non-partnered assets. Our approach to drug discovery and development has always been unique. What we refer to as a modality agnostic, target-driven research. Firstly, we identify high-impact targets. And in this case, we know that CD19 achieves broader coverage of the B cell compartment compared to CD20 or BCMA. So clearly, CD19 is the optimal target. Then we pursue the best approach to prosecute the chosen target. And in this case, a T cell engager likely provides the best therapeutic window and most patient convenient modality to address the target CD19 with multiple advantages over CAR-T cell therapy. CLN-978 is a very clear example of our unique approach in action and the molecule was engineered for optimal biological activity. In terms of the CLN-978 program, we plan to submit an IND in the third quarter of 2024, starting first with SLE, but continuing planning for development in other autoimmune diseases. I would also like to point out that members of our existing team have big immunology experience, which we're further augmenting by bringing in additional autoimmune disease expertise into the company through our recruitment efforts. While with discontinued enrollment in our lymphoma study, we did gather important clinical observations from the patients enrolled in the trial. The data clearly demonstrate that CLN-978 is a highly active molecule showing clinical activity at the first dose level with a favorable safety profile. Importantly, we also observed rapid, deep and sustained B cell depletion in patients. Jeff will cover these important new clinical data in further detail. On Slide 6, you can see our oncology pipeline remains on track. We have a highly differentiated pipeline across a range of cancer indications, giving us multiple near-term shots on goal. Our 2 highest priority programs, our CLN-978 in immunology and CLN-619, our MICA/MICB antibody in oncology, another potential first-in-class molecule addressing a novel pathway. We have a data-rich 2024 leading into the first half of 2025 with multiple data catalysts in the form of important clinical data readouts across our oncology programs. These includes readouts this quarter of the updated CLN-619 monotherapy data following the single agent efficacy we presented at ASCO last year, and for the first time, presentation of the combination data with pembrolizumab. Later this year, we plan to share additional clinical updates from Phase I clinical trials, the CLN-049, our FLT3xCD3 T Cell engager, which we're investigating in relapsed/refractory AML and high-risk MDS. And CLN-418, our B7H4x41BB bispecific immune activator, being investigated across a range of solid tumors. We also expect to have our zipalertinib pivotal study in relapsed exon 20 non-small cell lung cancer fully enrolled by the end of this year. As you can see, our transition from a research-based organization to a development stage company over the last 2 years has put us in a very strong position as we progress towards our goal of becoming a commercial stage biotech company. And with that, I will now hand it over to Dr. Jeff Jones to further discuss the important observations from our Phase I dose escalation study of CLN-978 in lymphoma as well as our development plans in autoimmune diseases. Jeff?

Thank you, Nadim. Beginning now with Slide #8. Summarized our data from a recently published New England Journal of Medicine paper describing the remarkable clinical experience of 15 patients treated with CD19 CAR-T therapy for the autoimmune diseases, systemic lupus erythematosus or SLE, idiopathic inflammatory myositis and systemic sclerosis. All the patients with SLE or myositis experienced a complete resolution of their disease symptoms. While the systemic sclerosis patients demonstrated reduced severity of skin and lung disease. Importantly, all patients were able to stop taking chronic and immunosuppressive medications without experiencing relapse or worsening of disease-related symptoms. These impressive results were achieved through an immune system [ reset ], characterized by rapid deep depletion of B cells followed by sustained reduction in the auto antibodies characteristic of the respective diseases despite recovery of normal B lymphocytes. Slide #9 highlights the safety profile of administering CD19 CAR-T therapy to these autoimmune patients. The safety profile of CD19 CAR-T therapy was generally favorable compared to what has been observed in oncology indications. However, infectious complications in part caused by the lymphodepleting chemotherapy regimen most likely were frequently observed. 14 of 15 patients experienced urinary tract or respiratory tract infections and 2 patients experienced herpes zoster virus reactivation. Important limitation with cell therapy for non-oncology indications are summarized on Slide 10. Currently available CAR-T therapies require lymphodepleting chemotherapy, which has been associated with increased risk for infection, infertility and secondary malignancies. A further risk for secondary hematologic malignancies is related directly to the CAR-T cells themselves as reflected by a recent FDA mandate to include boxed warnings on all approved CAR-T labels. Manufacturing lead times, reimbursement challenges and the need to administer cell therapies in specialized treatment centers, all limit patient access. This constellation of logistical and economic challenges may render retreatments upon relapse, an unlikely option for most patients. We often get asked whether T cell redirection by a T cell engager can achieve deep eradication of tissue-resident B cells. In fact, B-Cell Non-Hodgkin Lymphoma typically occurs in extra lymphatic tissues in many patients. Shown here on Slide 11, is the efficacy of 3 approved therapies for third line plus patients with follicular lymphoma. 2 of them CAR-T therapies and 1 of them, the T cell engager, Mosunetuzumab. As seen here, these 3 therapies have comparable efficacy as measured by either overall or complete response rate, evidencing similar activity in tissues beyond the peripheral blood. Now moving to Slide #12. Let me share a bit about CLN-978, a CD19xCD3 T cell engager that Cullinan created to deliver the potency of a T cell redirecting therapy but with off-the-shelf convenience. Designed to achieve high affinity binding to CD19, the molecule potently lysis CD19 expressing target cells, including those with very low levels of CD19 expression. The relative binding affinity of CD19xCD3 was further optimized to maximize the therapeutic index. Finally, the overall structure of the molecule was similar to a standard [indiscernible] has been refined to include an albumin binding modality to expand serum half-life. The molecule was also designed for patient-friendly subcutaneous administration. Slide #13 explains why we believe CD19 represents the optimal target to achieve the broad and deep B cell depletion needed to effect an immune system reset. Unlike CD20 and other B cell targets, CD19 achieves the broadest coverage of the B cell compartment extending from pro B cells to plasma blasts and even some mature plasma cells. The cell is primarily responsible for autoantibody production, notably and unlike BCMA, CD19 is not expressed on the long-lived plasma cells that play a crucial role in maintaining humoral memory and long-term immunity. On Slide #14, we depict a unique space, we believe, CLN-978 occupies among therapies currently under investigation for autoimmune diseases. While there are many cellular therapies and antibodies targeting CD19. CLN-978 has limited competition in the CD19 T cell engager space. And while there are CD20 T cell engagers in development for autoimmune indications, the CD20 target addresses a narrow portion of the B-cell lineage and also it spares the auto antibody-producing plasma cells, as I've just discussed. Let's now turn to some of the preclinical data that generated our initial enthusiasm for the potential of CLN-978 in autoimmune diseases. On the left-hand side of Slide #15, note that a single dose of CLN-978 induces rapid and deep depletion of B cells in nonhuman primates that is sustained for at least one month. The right-hand panels of the same slide further demonstrate that the induction of cytokine release observed when CLN-978 is given intravenously, can be attenuated by subcutaneous administration. This is an important feature of subcutaneous administration that we believe will greatly improve patient tolerability. From an important pharmacodynamic marker of B cell-depleting therapies, available data suggests that depletion of peripheral blood B cells is likely not sufficient to induce the immune system reset observed after T cell redirecting therapies. The additional nonhuman primary data shown on Slide #16, demonstrate that CLN-978 also produces deep B cell depletion into bone marrow, spleen and various lymphoid tissue, including visceral lymph tissue in the gut lining. Clinical observations from our Phase I dose escalation study of CLN-978 in B-Cell Non-Hodgkin Lymphoma replicate these preclinical observation. Slide #17 summarizes key data for the 3 patients treated at the initial starting dose of CLN-978 in the lymphoma study, 30 micrograms administered subcutaneously once weekly. The slide is dense, so I will walk you through the data. Firstly, 2 of these 3 patients experienced objective clinical benefit including 1 patient who experienced a complete response. We believe the observation of clinical benefit in patients with a tissue resident disease like lymphoma, bodes well for the prospect of achieving the type of immune system reset needed to benefit patients with autoimmune diseases. Equally as important, 30 micrograms of CLN-978 administered subcutaneously once weekly, had a favorable safety profile with maximum grade 1 cytokine release syndrome, or CRS, observed in 2 patients and no immune effector cell-associated neurotoxicity syndrome, also known as ICANS. CRS and ICANS toxicities typically associated with both cellular therapy and T cell engagers. For the 2 patients who experienced grade 1 CRS events, the events occurred only following the first infusion and did not reoccur with subsequent doses. In both cases, patients experienced a low-grade fever, which was treated with acetaminophen. The fevers resolved within 4 hours without the need for any additional intervention. Patient #3, who experienced a complete response to therapy, experienced transient grade 1 tremor concurrent with acute influenza infection. Within 48 hours after treatment with antiviral medication and corticosteroids, the flu symptoms and tremor resolved. Conservatively, the investigator elected to continue steroid medication with subsequent injections, but the steroid treatment was tolerated poorly. This patient subsequently experienced intermittent grade 2 restlessness and an episode of transient grade 2 confusion that was resolved within 24 hours. Patient 3 also experienced a vascular access complication, a deep venous thrombosis associated with an ingrown catheter. This patient has a history of venous thromboembolic disease and the investigator deemed the [ event ] unrelated to study drug. In terms of the hematologic adverse events, all 3 patients experienced an expected transient lymphopenia following administration of the first dose of CLN-978. This first dose effect is mechanistically based and a common observation at pharmacologically active doses of T cell engagers attributable to T cell margination and recruitment. More simply stated, this is only a transient redistribution effect. T cell counts have returned to baseline within 96 hours following the first dose. So this transient lymphopenia is not expected to increase the risk for infection. Other adverse events observed on this study were low grade. While one patient continues to receive study treatment as of the April set data cutoff, we have otherwise discontinued further enrollment for the lymphoma study to reprioritize development of CLN-978 in autoimmune disease. But pictures, as they say, are worth a thousand words. Baseline and posttreatment scans for subject #3, a patient with mantle cell lymphoma who had received 3 prior lines of treatment, including high-dose chemotherapy and autologous stem cell transplant are shown on Slide #18. At baseline, a mass measuring 7.4 x 1.7 centimeters replaces the patients left mandibular ramus and extends into the adjacent muscles. The treating physician reported that the mass was no longer appreciated in a clinical exam, 96 hours after administration of the first dose of CLN-978. And as these PET images obtained after 7 doses show, the mass was markedly less metabolically active after treatment, consistent with a complete response to therapy. Moving now to Slide #19. You can see that CLN-978 treatment achieved rapid, deep and sustained B cell depletion in both patients who had measurable levels of B cells in the peripheral blood at baseline. In subject 1, who received 9 doses of CLN-978, B cell depletion was maintained for several months, following the last dose of study drug. Now on Slide #20, we review key features of our planned study of CLN-978 and SLE, which will be the first autoimmune disease indication we study. The study will begin with a limited dose escalation phase that incorporates step-up dosing and standard premedications to minimize the risk for CROs. Once we determine our dose for further testing, we will then further explore safety and preliminary efficacy in a larger number of SLE patients. During that expansion phase of the study, 2 or more dosing schedules may be explored. We are currently analyzing our data to determine the planned dose and dosing schedule as we prepare to submit the IND in the third quarter of this year. And now I'll turn it back over to Nadim.

Thank you, Jeff. On Slide 21, you can see that SLE continues to affect a significant number of patients and effective therapies remain limited. In the U.S. alone, we estimate that more than 120,000 patients could potentially benefit from novel therapies like CLN-978. The issue with current standard of care is that they largely alleviate symptoms and do not address the underlying pathophysiology of the disease, which means most patients require lifelong immunosuppression and are not able to experience treatment-free remission. Far too many of these patients go on to develop lupus nephritis, which can lead to end organ failure and sometimes death. Despite the fact that available treatments like Benlysta or Saphnelo, largely alleviate symptoms rather than address the underlying disease. These 2 drugs still managed to achieve an estimated $1.5 billion in 2023 U.S. sales. However, by our own estimates, based on the epidemiology data, the total addressable market in the U.S. for moderate to severe SLE patients is in excess of $11 billion, representing a compelling market opportunity for a potential disease-modifying therapy like CLN-978. Where we see the opportunity of CLN-978 is graphically represented on Slide 22. On the left-hand side of the graph, are the current standard of care, which have modest efficacy and generally require patients to remain on continuous immunosuppression therapy. On the other hand, the early data we have seen so far for CD19 CAR-T appears at the other end of the scale, highly efficacious without the need for continuous immunosuppression. However, for all of the reasons we discussed earlier, we believe CAR-T will likely be reserved for sicker, more refractory patients. As a result, this leaves a very large opportunity gap for CLN-978 between the outcomes associated with current standard of care and up to those of CAR-T therapy. Through extensive discussions of [indiscernible], one very important insight we have gained is that as long as CLN-978 delivers outcomes that are significantly better than current standard of care. In other words, to the right of current treatments in the graph, it has the potential for widespread adoption across multiple patient segments. While lupus will be the first automine indication in which we developed CLN-978, Slide 23 lists many additional autoimmune diseases that have the potential to be addressed by a B cell depleting T cell redirecting therapy, and we've given careful consideration to many of these additional diseases as part of the overall development plan for CLN-978. Finally, in conclusion, on Slide 24, the Cullinan Therapeutics team committed to expeditiously exploring the full potential of CLN-978 for patients living with autoimmune diseases. We firmly believe that T Cell redirection therapies CAR-T CD19 are an incredibly promising way to achieve the powerful immune system reset that can potentially modify the course of not only SLE, but many other autoimmune diseases. And as a potential first-in-class opportunity, CLN-978 is differentiated by off-the-shelf convenience and patient-friendly subcutaneous administration, with the potential to deliver potent disease-modifying effects with a favorable safety profile. And as demonstrated in patients with B cell lymphoma, CLN-978 can achieve rapid, deep and prolonged B cell depletion, not only in the peripheral blood, but also in tissue. We were also very pleased to see clinical activity, including remarkably a complete response at the initial starting dose of 30 micrograms. In terms of next steps, we intensified an IND for SLE in Q3 of this year. And for us, SLE is only the starting point of the story. As we explore the full potential for CLN-978 to favorably impact the life of patients living with many other autoimmune diseases. Thank you for your attention, and I will now turn the call over to the operator and ask Jeff and Patrick to join me to take your questions.

[Operator Instructions] The first question comes from Jeffrey Hung with Morgan Stanley.

This is Katherine on for Jeff. Congrats on the updates today. Can you talk about your expectations for therapeutic dose range for SLE and how that compares to the starting dose study that you study for B-NHL?

Thanks, Katherine, for your questions [indiscernible]. I'll ask Jeff to address that question.

Again, thank you very much for the question. I think it's premature, as Nadim shared in the call for us to provide specifics regarding the dose or range of doses we'll employ in the SLE and we point you to the fact that the 30 micrograms starting dose imploring the B cell non-Hodgkin lymphoma study, achieved rapid, deep and sustained B cell depletion with a favorable safety profile of no higher than grade 1 CRS. We also saw depletion of intra-tissue B cells in the case of the patients with complete response to therapy. So I think that gives a sense of the potential range over which the molecule is active. But again, specifics will be determined closer to the time of IND filing in Q3 of this year.

The next question comes from Andrew Berens with Leerink.

Congrats on the updates. Exciting times. I was wondering, are there any potential liabilities associated with the broader coverage seen with CD19 versus CD20? I think you showed that CD19 is expressed in plasma and Pro-B cells, but the CD20 is not? And then do you think that using a CD19 TC ahead of a CAR-T could limit the subsequent CAR-T activity?

Andy thank you for your questions. I will pass it over to Jeff.

Andy, [ based ] on those questions, and they are both 2 very interesting questions. So the first, in terms of the CD19 target itself, I think the observation from the CD19 CAR-T cell studies suggest that the breadth and depth of B cell depletion is actually what's necessary to achieve the immune reset that led to the treatment-free remission in patients with SLE and other autoimmune disorders. So I think the important consideration there is twofold, one that sustained B cell depletion beyond several months on -- in that case, is probably not necessary for the effect and there you might need patients at risk for infections if that degree of B cell depletion was chronic. And number two, CD19 spares long-lived plasma cells that do express BCMA for instance. So there, the observation from the CAR-T trials and what I would expect to hold true for TCEs is that long-lived humoral immune responses including vaccine responses will be preserved with the CD19 target. In terms of your second question, could you just repeat that one for me?

Yes, I'm just wondering is targeting CD19 or the TCE ahead of CAR-T therapy could [ win ] a subsequent CAR-T activity?

Yes. I don't think that's likely. I mean, certainly, in the case of oncologic indications where there's selected pressure on malignant clones that might be lower in expression of CD19. You do see emergence of resistance to CD19-directed therapies. But in normal B cells and normal cells of B-cell lineage, I wouldn't expect any such phenomenon to hold. [indiscernible].

Yes. Can I just sneak one more in. I just -- I know you showed us the study design, it's early days, but is the goal to reset the immune system and then stop therapy? Or is this something that you think would be a chronic administration maybe with the -- would it be chronically administered? Or is it possible that it could be stopped and then retreated [indiscernible]?

It's a good question. I think that the observation again, at least an SLE and the other diseases in their [indiscernible] share data is that transient [indiscernible] can affect an immunes reset. In that case, you might consider dosing 978 for defined duration of period, and defined duration of treatment that achieves a similar degree of B cell depletion might be appropriate. I think one of the things about TCE versus CAR-T is that one preserves a lot of opportunity for different dosing schemes. And number two, it does lend itself to the potential for retreatment as the reemergence of disease symptoms or other related findings like perhaps autoantibodies production. Maybe in other disorders, the dosing paradigm might be different, but it means the TCE lends itself to that degree of dosing flexibility unlike CAR T.

Our next question comes from Marc Frahm with TD Cowen.

Congrats on all the updates today. Maybe just following up on Andy's last question. Just what are those plans on kind of time-limited therapy in the initial trial? Is that kind of the initial design of your dosing theme? Or is that something you'll kind of only add in later trials, trying to stop therapy if you're seeing the types of durable responses that we're seeing so far in the CAR-T cell space?

Marc, thanks for your question. Jeff, would you like to take that one?

Sure. Again, I would just stress that the final doses and schedules that we include in the SLE trial will be finalized closer to IND, probably in the Q3. But I will state that I believe at the outset, we will be thinking more about the fine duration of therapy on that duration to be determined on the part by ongoing analysis of our existing PK/PD data as well as data that would be generated in the dose acquisition phases of an SLE trial, but I don't anticipate in this first study that we would be dosing or continue the schedule unlike oncology.

That's helpful. And then maybe just think through -- as we start to get data out, what do you need to see out of this trial in SLE to kind of start opening up some of those other opportunities that you showed on one of the last slides of all these other autoimmune diseases that are B cell driven.

Yes. I think, Marc, it's not any specific but first, I'd say, no specific finding from the SLE trial is gating for exploring those other indications. I think just as we make this important strategic pivot, this is where we're starting, but we would ultimately like to explore a number of different indications in parallel. That said, in terms of what we might expect to see in an SLE trial. I think it's the whole constellation of things both symptom scores, patient efficacy measures, auto antibody titers and other serologic findings like complement levels as well as typical PK/PD relationships, most importantly, the degree of peripheral B-cell application using a very sensitive asset.

Yes, Marc, I would add to what Jeff said, one of the key focus areas of the proceeds in the [indiscernible] are going to be to optimize the full potential of CLN-978. So what does that mean? What it means if allows us to expand our development plan across multiple indications, but also allows us to conduct studies more in parallel rather than sequentially to Jeff's point. So there aren't necessarily gating features of the lympho study before we would embark on other indication. So just wanted to make that clear also.

[Operator Instructions] Our next question comes from Kaveri Pohlman with BTIG.

Congrats on the update. So the clinical data so far is from lymphoma, which is clearly a high burden disease. Can you tell us how you're going to utilize your learning, especially in terms of building strategy to target SLEs?

Thanks, Kaveri for your question. Jeff?

Kaveri. Yes, it's a great question, and I think I'd just point you back to the key clinical observations. The first is that a single dose of CLN-978 have achieved deep in rapid B-cell solution, rapid meaning, it was observable by [ per-covalent ] flow 96 hours after a single dose. And so I think we understand as well that, that dose is at the threshold of efficacy for non-Hodgkin's lymphoma, in which case it is sufficient to achieve a complete response in the patients with quite refractory mantle cell lymphoma. So if you think about that, it provides a very clear understanding that at a dose that has a favorable safety profile with no higher than grade 1 CRS. We are probably achieving defines of outcomes that would be necessary to achieve the therapeutic effect in SLE, where you are expecting rapid and deep B cell depletion, including depletion of B cells in the tissue. And I think we've been able to show that quite surprisingly in a first-in-human study at the starting dose. We've been able to show that, as you say, in a place where it's probably more difficult to achieve than in autoimmune disease.

And how big of a concern CRS is for autoimmune diseases, given that you don't really have to push those hard to control a rapidly progressing [indiscernible] disease like cancer?

Yes. I think that observation is correct. And if you look at the CAR-T data, you'll see that the safety profile for CAR-T appears to be more favorable than has been observed at similar doses and oncologic indications. And I think that's right. It's both the burden of disease, rapidly growing disease, that then develop to more severe cytokine disease and oncologic applications of T cell redirecting approaches. And I think something similar will hold for TCE. And I think even [indiscernible] we see it would be our hope that we could demonstrate an even more favorable safety profile in autoimmune diseases. But of course, that's a clinical experiments that we will do with the SLE trial.

Got it. And maybe a quick one. Can you tell us how many additional indications besides SLEs you plan to persue for 978?

Yes. Let me take that one, Kaveri. As you can imagine, it's a topic of intense discussion within the company at the moment. Right now, we're focused on submitting the SLE by third quarter indication by first quarter of this year. And once we've identified additional indications that we plan to pursue, we'll make that name at the right time.

The next question comes from Soumit Roy with Jones Trading.

Congratulations on all the data. On the strategic front for the next 2 to 3 years and especially with the change in name of the company to Therapeutics, do we expect the 978, asset to be kept in-house rather than being partnered out? Or -- and should we think opportunities beyond oncology could become the next focus?

Thanks, Soumit for your question. Yes. So I would say with our strategic expansion into autoimmune diseases, we're now a company that is active in both oncology and immunology, which I do think is an excellent strategic fit, given the fact that we're focused on discovering those patterns today in oncology and immunology. So going to have some of that expertise which we further [ strengthen ]. So for now, it's oncology and immunology. And I would say that we're very fortunate, including with the new ray that we have the human and financial resources to progress CLN-978 at this point in time.

Understood. And on 619 front, potentially midyear update, what can you tell us about expected cohort size, duration of follow-up, what is the maximum KEYTRUDA combination arm dosage being administered already? Any color would be appreciated.

Jeff, would you like to take that one?

Sure. So we expect to present the totality of data from the dose escalation phase of the trial, inclusive of both the first presentation of the combination arm of the trial as well as an update on our monotherapy experience that was first presented last year at ASCO 2023. We had a handful of patients above the 37 that we reported for monotherapy last year, yet to accrue and that will be incremental in terms of patient totals for monotherapy and about half as many in the combination are where we started several dose levels higher for the dose escalation. In both arms of the trial, we discontinued the dose escalation for plan at 10 milligrams per kilogram for CLN-619.

At this time, I am showing no further questions. I would now like to turn the call back to Nadim Ahmed, Cullinan's Chief Executive Officer, for closing remarks.

Thanks, Michelle. I will just repeat again, today is a really exciting new chapter for our company as we add immunology, a new therapeutic area for us, which obviously have excellent strategic fit, given our expertise in immuno-oncology. And the second time, we're really looking forward to developing CLN-978 expeditiously, as an off-the-shelf potential disease lifetime treatment across a range of autoimmune diseases. So thank you, everyone, for dialing in, and we'll be in touch.

This concludes today's conference call. Thank you for your participation. You may now disconnect.